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Movement disorders
Published in Henry J. Woodford, Essential Geriatrics, 2022
Drugs with anticholinergic properties may worsen cognition. Withdrawal of medications as outlined in Table 9.1 should be considered. Cholinesterase inhibitors have been tried in the treatment of PDD. A group of 541 people with PDD (mean age 73; mean MMSE score 19) received either rivastigmine or placebo over a 24-week period.84 There was a small but statistically significant difference in ADAS-cog scores (see Appendix A) of 2.8 (out of 70) in favour of the rivastigmine group. However, the clinical significance of this degree of change is questionable and differential drop-out rates may have accounted for some of the difference. Also, there were significantly more adverse effects observed in the treatment arm. Those occurring more commonly with rivastigmine compared to placebo included nausea (29% v 11%), vomiting (17% v 2%) and tremor (10% v 4%). A systematic review (4 studies; total n = 941; mean age 72; mean MMSE 20; mean follow-up 24 weeks) found a small benefit in cognition (MMSE difference 1.1; 95% CI 0.6–1.6) but increased tremor (OR 2.8; 95% CI 1.5–5.6) and overall adverse drug reactions (OR 1.9; 95% CI 1.3–2.6).85 There was no effect on behavioural disturbance. In addition, the authors detected a risk of reporting bias regarding the cognitive outcome. These data do not appear to justify the routine use of cholinesterase inhibitors in PDD. However, current guidance allows consideration of a cholinesterase inhibitor, or memantine if not tolerated, for this indication.7
Cognition Enhancers
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Ramneek Kaur, Rashi Rajput, Sachin Kumar, Harleen Kaur, R. Rachana, Manisha Singh
The cognition enhancers can have various side effects via body system other than the brain. Memantine (NMDA receptor antagonist) and acetylcholinesterase inhibitors (AChEIs) are used as a standard treatment therapy for various NDs like AD and PD can cause nausea or gastrointestinal upset, thereby, leading to discontinue the treatment altogether. These consequences have the ability to counteract the positive effect of the drug on the overall performance. Donepezil and rivastigmine are used to treat dementia with Parkinson’s disease dementia (PDD) and Lewy bodies (DLB). It is seen that rivastigmine in healthy patients improve learning and helps in making association between digits and symbols, but at the same time, it can impair visual and verbal episodic memory. Bromocriptine is a dopamine agonist that can increase spatial working memory (WM) yet, also impair probabilistic reversal learning. The outcome echoes the outcomes in patients with PD, the dopamine receptor agonist helps to improve the WM and task-set switching tasks yet, degrades the reversal learning (RL) (Swainson et al., 2000; Cools et al., 2001). It is hypothesized that these divergent effects are because of the replenishment of dopamine in dorsal striatal areas required for the anterior and overdosing of ventral striatal areas involved in the end. Therefore, the doses of dopaminergic medication play an integral role to improve the functioning of motor neuron and some features have the ability to worsen others.
Medication and dementia
Published in Graham A. Jackson, Debbie Tolson, Textbook of Dementia Care, 2019
These drugs are not licensed for use in patients with purely vascular dementia, but can be used in those with mixed Alzheimer’s and vascular disease. Rivastigmine is also licensed for use in dementia in Parkinson’s disease.
An update on the utility and safety of cholinesterase inhibitors for the treatment of Alzheimer’s disease
Published in Expert Opinion on Drug Safety, 2020
Andrea Haake, Kevin Nguyen, Lauren Friedman, Binu Chakkamparambil, George T Grossberg
In terms of gastrointestinal side effects, a meta-analysis showed rivastigmine at doses of 1–4mg/day and 6–12mg/day was associated with higher rates of nausea, vomiting, diarrhea, weight loss, anorexia, and decreased appetite when compared to placebo [59]. These side effects may be due to increased cholinergic neurotransmission from the drug’s dual cholinesterase inhibition, as well as direct stimulation of muscarinic receptors of the chemoreceptor trigger zone of the area postrema [60]. Moreover, adverse symptoms of rivastigmine tend to be more common during the titration phase of treatment and decrease with the maintenance phase [43,46]. To reduce side effects, rivastigmine should be slowly titrated and taken with food, particularly a fatty meal, which would delay absorption from the gut (prolonging tmax) and reduce fluctuations in plasma concentration associated with adverse events [61]. If the medication is stopped for more than 3 days, the titration phase should be restarted at the lowest dose to prevent severe vomiting that could lead to Boerhaave’s syndrome [44]. In 2000, a case report was published describing spontaneous esophageal rupture in a female with AD treated with rivastigmine [62]. She accidentally reinitiated treatment with an oral 4.5mg dose, and was found to have a distal esophageal rupture. Following the event, the package insert was amended to include warning of esophageal rupture.
Preparation and optimization of rivastigmine-loaded tocopherol succinate-based solid lipid nanoparticles
Published in Journal of Liposome Research, 2018
Fariba Malekpour-Galogahi, Ashrafalsadat Hatamian-Zarmi, Fariba Ganji, Bahman Ebrahimi-Hosseinzadeh, Fahimeh Nojoki, Razi Sahraeian, Zahra Beagom Mokhtari-Hosseini
Rivastigmine, an inhibitor of acetylcholine and butyrylcholinesterase, is currently used to manage mild-to-moderate Alzheimer’s disease (AD), which is a progressive neurodegenerative disorder of the central nervous system (CNS) (Yang et al. 2013, Alzheimer’s 2015, Lavon et al. 2015). However, the problem is that the blood–brain barrier (BBB) limits hydrophilic rivastigmine’s reaching the brain (Blasi et al. 2007). More frequent dosing can act as a compensation for transmission limitations, but it may cause side effects such as severe bradycardia, nausea, dyspepsia, vomiting and anorexia (Yang et al. 2013). Drug delivery is a seemingly promising approach to overcome this problem, in that it provides a better framework for the effective delivery of such drugs to the CNS through enhanced access across the BBB (Srikanth and Kessler 2012).
Physiologically-based pharmacokinetic modeling for mirabegron: a multi-elimination pathway mediated by cytochrome P450 3A4, uridine 5'-diphosphate-glucuronosyltransferase 2B7, and butyrylcholinesterase
Published in Xenobiotica, 2019
Kentaro Konishi, Tsuyoshi Minematsu, Yasuhisa Nagasaka, Kenji Tabata
Some BChE inhibitors have been identified. For example, rivastigmine has been developed to treat Alzheimer’s disease (Jann et al., 2002). However, there are no available data that can be used in the Simcyp Simulator to predict the magnitude of the DDI between mirabegron and a BChE inhibitor. Therefore, to simulate a DDI between mirabegron and a BChE inhibitor, a sensitivity analysis was performed. When the half-life for BChE in plasma was increased by 10-fold (725 min) in the presence of a BChE inhibitor, Cmax and AUCinf were predicted to increase by only 2% and 5%, respectively. These results suggest that BChE inhibitors might have a negligible effect on the PK of mirabegron.